Interleukin-9 ("IL-9" hereafter), is a glycoprotein which has been isolated from both murine and human cells. See, e.g., U.S. Pat. No. 5,208,218, incorporated by reference. This reference also teaches isolated nucleic acid molecules encoding the protein portion of the molecule, and how to express it.
Various uses of the molecule can be seen in, e.g., U.S. Pat. No. 5,164,317 (proliferation of mast cells); U.S. Pat. Nos. 5,246,701 and 5,132,109 (enhancing production of IgG and inhibiting production of IgE), in addition to its first recognized utility, which is as a T cell growth factor. Exemplary of the vast scientific literature on the molecule are Van Snick, et al, J. Exp. Med. 169(1): 363-368 (1989) (cDNA for the murine molecule, then referred to as P40). Houssiau, et al, J. Immunol 148(10): 3147-3151 (1992) (IL-2 dependence of IL-9 expression in T lymphocytes). Renauld, et al, Oncogene 9 (5): 1327-1332 (1994) (effect on thymic lymphomas); Renauld, et al, Blood 85(5): 1300-1305 (1995) (anti-apoptotic factor for thymic lymphoma). Review articles may be found at, e.g., Renauld, et al, Cancer Invest 11(5): 635-640 (1993); Renauld, et al, Adv. Immunol 54: 79-97 (1993).
There is no literature on the influence of IL-9 on autoimmune disorders.
The art is familiar with a vast number of autoimmune disorders, which are classified in various ways. One way of classification is by way of the aspect of the immune system most intimately involved with the disorder. For example, in humoral response associated autoimmune diseases, B cells are involved. Antibodies are generated against self molecules, such as the acetylcholine receptor (myasthenia gravis), or the TSH receptor (Graves disease). In autoimmune diseases involving a cellular response, T cells, macrophages, and NK cells react with self molecules. Exemplary of these conditions are insulin dependent diabetes and thyroiditis. This family of diseases result, inter alia, from a skewing of Th1/Th2 balance.
One problem in the study of autoimmune diseases is the absence of suitable animal models. Without an appropriate system for studying a particular condition, one cannot draw conclusions as to the potential efficacy of a given drug in a therapeutic context.
An appropriate animal model for cell mediated diseases does exist, however, and it has been used in the disclosure which follows. Using the specific case of induced thyroiditis in a murine model, it has now been shown that IL-9 has therapeutic efficacy in Th1 associated autoimmune disorders. This will be shown in the detailed description of preferred embodiments which follows.
The murine model used in the disclosure which follows is also one which can be used to study diseases such as sialoadenitis, autoimmune hemolytic anemia, and other conditions. Further, a murine model is available which is useful in studying pathologies involving fibrosis, such as interstitial lung disease. Characteristic of these fibrosis related pathologies is inflammation in the afflicted tissue or organ, leading to scarring and distortion of tissue. Exemplary of this group of pathologies are interstitial lung diseases such as silicosis, asbestosis, white lung disease, black lung disease, Shaver's disease, etc. These conditions are known as pneumoconioses, (or anthracotic tuberculosis), and involve inflammation and lung fibrosis, caused, e.g., by inhalation of fine mineral particles. Other fibrotic conditions include all forms of sclerosis, fibrosis related rheumatism, such as chronic rheumatoid arthritis, and collagen related fibrosis, such as conditions involving keloids, scarring, renal diseases involving related conditions, and so forth.
The murine models for these conditions have been employed, as will be seen infra, to show the efficacy of IL-9 in their treatment.